Multidrug resistance (MDR) is a major reason for the clinical failure of many forms of chemotherapy. In the past few decades, a number of different mechanisms were found to mediate the development of MDR, and among which the most important were those associated with the overexpression of various ATP binding cassette (ABC) transport proteins. Permeability glycoprotein 1 (abbreviated as P-gp), also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1), is the most extensively studied ABC transporter protein, which is significantly elevated in drug-resistant tumors and pumps out various anticancer drugs, such as taxanes, anthracyclines, vinca alkaloids, and epipodophyllotoxins. Since 1981, P-gp inhibitors have been intensively studied as potential MDR reversers. However, while several P-gp inhibitors were found among the available drugs, they have the disadvantage of toxicity and poor drug interaction profiles. Therefore, new and more effective compounds with low toxicity and fewer side effects are desirable.